European Heart Journal (2012) 33, 1635–1701 doi:10.1093/eurheartj/ehs092 JOINT ESC GUIDELINES European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)† Authors/Task Force Members: Joep Perk (Chairperson) (Sweden)*, Guy De Backer ˇ eljko Reiner (Belgium), Helmut Gohlke1 (Germany), Ian Graham (Ireland), Z (Croatia), W.M Monique Verschuren1 (The Netherlands), Christian Albus (Germany), Pascale Benlian (France), Gudrun Boysen (Denmark), Renata Cifkova (Czech Republic), Christi Deaton (UK), Shah Ebrahim (UK), Miles Fisher (UK), Giuseppe Germano (Italy), Richard Hobbs 1,7 (UK), Arno Hoes (The Netherlands), Sehnaz Karadeniz (Turkey), Alessandro Mezzani (Italy), Eva Prescott (Denmark), Lars Ryden (Sweden), Martin Scherer (Germany), Mikko Syvaănne9 (Finland), Wilma J.M Scholte Op Reimer (The Netherlands), Christiaan Vrints (Belgium), David Wood (UK), Jose Luis Zamorano1 (Spain), Faiez Zannad (France) Other experts who contributed to parts of the guidelines: Marie Therese Cooney (Ireland) ESC Committee for Practice Guidelines (CPG): Jeroen Bax (Chairman) (The Netherlands), Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK), Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (The Netherlands), Paulus Kirchhof (Germany), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK), Cyril Moulin (France), ˇ eljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Bogdan A Popescu (Romania), Z Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian (France), Stephan Windecker (Switzerland) Document Reviewers: Christian Funck-Brentano (CPG Review Coordinator) (France), Per Anton Sirnes (CPG Review Coordinator) (Norway), Victor Aboyans (France), Eduardo Alegria Ezquerra (Spain), Colin Baigent (UK), * Corresponding author: Joep Perk, School of Health and Caring Sciences, Linnaeus University, Stagneliusgatan 14, SE-391 82 Kalmar, Sweden Tel: +46 70 3445096, Fax: +46 491 782 643, Email: joep.perk@lnu.se † Other ESC entities having participated in the development of this document: Associations: European Association of Echocardiography (EAE), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA) Working Groups: Acute Cardiac Care, e-Cardiology, Cardiovascular Pharmacology and Drug Therapy, Hypertension and the Heart Councils: Basic Cardiovascular Science, Cardiology Practice, Cardiovascular Imaging, Cardiovascular Nursing and Allied Professions, Cardiovascular Primary Care The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only No commercial use is authorized No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC Disclaimer The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written Health professionals are encouraged to take them fully into account when exercising their clinical judgement The guidelines not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’s guardian or carer It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines & The European Society of Cardiology 2012 All rights reserved For permissions please email: journals.permissions@oxfordjournals.org 1636 Joint ESC Guidelines Carlos Brotons (Spain), Gunilla Burell (Sweden), Antonio Ceriello (Spain), Johan De Sutter (Belgium), Jaap Deckers (The Netherlands), Stefano Del Prato (Italy), Hans-Christoph Diener (Germany), Donna Fitzsimons (UK), Zlatko Fras (Slovenia), Rainer Hambrecht (Germany), Piotr Jankowski (Poland), Ulrich Keil (Germany), Mike Kirby (UK), Mogens Lytken Larsen (Denmark), Giuseppe Mancia (Italy), Athanasios J Manolis (Greece), John McMurray (UK), Andrzej Paja˛k (Poland), Alexander Parkhomenko (Ukraine), Loukianos Rallidis (Greece), Fausto Rigo (Italy), Evangelista Rocha (Portugal), Luis Miguel Ruilope (Spain), Enno van der Velde (The Netherlands), Diego Vanuzzo (Italy), Margus Viigimaa (Estonia), Massimo Volpe (Italy), Olov Wiklund (Sweden), Christian Wolpert (Germany) The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines Societies: 1European Society of Cardiology (ESC); 2European Atherosclerosis Society (EAS); 3International Society of Behavioural Medicine (ISBM); 4European Stroke Organisation (ESO); 5European Society of Hypertension (ESH); European Association for the Study of Diabetes (EASD); 7European Society of General Practice/Family Medicine (ESGP/ FM/WONCA); 8International Diabetes Federation Europe (IDF-Europe); 9European Heart Network (EHN) Online publish-ahead-of-print May 2012 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords Cardiovascular disease † Prevention † Risk assessment † Risk management † Smoking † Nutrition † Physical activity † Psychosocial factors Table of Contents Abbreviations and acronyms 1638 What is cardiovascular disease prevention? 1638 1.1 Introduction 1638 1.2 Development of guidelines 1639 1.3 Evaluation methods 1639 1.4 Combining evaluation methods 1640 Why is prevention of cardiovascular disease needed? 1641 2.1 Scope of the problem 1641 2.2 Prevention of cardiovascular disease: a lifelong approach 1642 2.3 Prevention of cardiovascular disease pays off 1642 2.4 Ample room for improvement 1643 Who should benefit from it? 1644 3.1 Strategies and risk estimation 1644 3.1.1 Introduction 1644 3.1.2 Strategies 1645 3.1.3 Risk estimation 1646 3.2 Genetics 1652 3.3 Age and gender 1652 3.4 Psychosocial risk factors 1653 3.4.1 Risk factors 1653 3.4.2 Clustering of psychosocial risk factors and bio-behavioural mechanisms 1654 3.4.3 Assessment of psychosocial risk factors 1654 3.5 Other biomarkers of risk 1655 3.5.1 Inflammatory: high-sensitivity C-reactive protein, fibrinogen 1655 3.5.2 Thrombotic 1656 3.6 Imaging methods in cardiovascular disease prevention 1656 3.6.1 Early detection by magnetic resonance imaging of cardiovascular disease in asymptomatic subjects 1657 3.6.2 Coronary calcium score 1657 3.6.3 Carotid ultrasound 1657 3.6.4 Ankle – brachial index 1658 3.6.5 Ophthalmoscopy 1658 3.7 Other diseases with increased risk for cardiovascular disease 1658 3.7.1 Influenza 1658 3.7.2 Chronic kidney disease 1658 3.7.3 Obstructive sleep apnoea 1659 3.7.4 Erectile dysfunction 1659 3.7.5 Autoimmune diseases 1659 3.7.5.1 Psoriasis 1659 3.7.5.2 Rheumatoid arthritis 1659 3.7.5.3 Lupus erythematosus 1659 3.7.6 Periodontitis 1659 3.7.7 Vascular disease after radiation exposure 1659 3.7.8 Vascular disease after transplantation 1659 How can cardiovascular disease prevention be used? 1660 4.1 Principles of behaviour change 1660 4.1.1 Introduction: why individuals find it hard to change their lifestyle? 1660 4.1.2 Effective communication and cognitive-behavioural strategies as a means towards lifestyle change 1660 4.1.3 Multimodal, behavioural interventions 1661 4.2 Smoking 1661 4.2.1 Introduction 1661 4.2.2 Dosage and type 1662 4.2.3 Passive smoking 1662 4.2.4 Mechanism by which tobacco smoking increases risk 1662 4.2.5 Smoking cessation 1662 4.2.6 Pharmacological aids 1664 4.2.7 Other smoking-cessation interventions 1664 Joint ESC Guidelines 4.3 Nutrition 1664 4.3.1 Introduction 1665 4.3.2 Nutrients 1665 4.3.3 Foods and food groups 1666 4.3.4 Functional foods 1667 4.3.5 Dietary patterns 1667 4.4 Physical activity 1668 4.4.1 Introduction 1668 4.4.2 Biological rationale 1668 4.4.3 Healthy subjects 1669 4.4.4 Patients with known cardiovascular disease 1670 4.5 Management of psychosocial factors 1671 4.5.1 Introduction 1671 4.5.2 Specific interventions to reduce depression, anxiety, and distress 1671 4.6 Body weight 1672 4.6.1 Introduction 1672 4.6.2 Body weight and risk 1672 4.6.3 Which index of obesity is the best predictor of cardiovascular risk? 1672 4.6.4 The obesity paradox in established coronary artery disease 1673 4.6.5 Treatment 1673 4.7 Blood pressure 1674 4.7.1 Introduction 1675 4.7.2 Definition and classification of hypertension 1675 4.7.3 Diagnostic evaluation 1675 4.7.4 Blood pressure measurement 1675 4.7.5 Office or clinic blood pressure measurement 1675 4.7.6 Ambulatory and home blood pressure monitoring 1676 4.7.7 Risk stratification in hypertension 1676 4.7.8 Who to treat, and when to initiate antihypertensive treatment 1677 4.7.9 How to treat 1678 4.8 Treatment targets in patients with type diabetes 1680 4.8.1 Introduction 1681 4.8.2 Evidence for current recommendations on cardiovascular disease prevention in diabetes 1681 4.8.3 Glucose control 1681 4.8.4 Glucose targets 1681 4.8.5 Meta-analysis and systematic reviews 1681 4.8.6 Blood pressure 1681 4.8.7 Dyslipidaemia 1682 4.8.8 Antithrombotic therapy 1682 4.8.9 Microalbuminuria and multifactorial intervention 1682 4.9 Lipids 1683 4.9.1 Introduction 1683 4.9.2 Low-density lipoprotein cholesterol 1683 4.9.3 Apolipoprotein B 1684 4.9.4 Triglycerides 1684 4.9.5 High-density lipoprotein cholesterol 1684 4.9.6 Lipoprotein(a) 1684 4.9.7 Apolipoprotein B/apolipoprotein A1 ratio 1684 4.9.8 Calculated lipoprotein variables 1684 1637 4.9.9 Exclusion of secondary dyslipidaemia 1685 4.9.10 Who should be treated and what are the goals? 1685 4.9.11 Patients with peripheral artery disease 1686 4.9.12 Stroke prevention 1686 4.9.13 Patients with kidney disease 1686 4.9.14 Transplant patients 1686 4.9.15 Patients with an acute coronary syndrome 1686 4.9.16 Drugs 1686 4.9.17 Drug combinations 1687 4.9.18 Low-density lipoprotein apheresis 1687 4.10 Antithrombotics 1688 4.10.1 Antiplatelet therapy in individuals without overt cardiovascular disease 1688 4.10.2 Antiplatelet therapy in individuals with overt cardiovascular or cerebrovascular disease 1688 4.10.3 Antithrombotic therapy in atrial fibrillation 1689 4.11 Adherence 1689 4.11.1 Why patients not adhere to prescribed medication? 1689 Where should programmes be offered? 1690 5.1 Cardiovascular disease prevention in primary care: role of nurses 1691 5.1.1 Nurse-co-ordinated prevention programmes effective in various healthcare systems 1691 5.1.2 Sustained contact is necessary for lifestyle change 1691 5.2 Cardiovascular disease prevention in general practice 1692 5.2.1 Identifying individuals at risk 1692 5.2.2 Use of risk scoring in clinical practice 1692 5.2.3 Barriers to implementing routine risk assessment 1693 5.2.4 Methods for improving awareness and implementation of risk scoring 1693 5.2.5 Better risk factor management 1693 5.3 Cardiovascular disease prevention in primary care: role of the cardiologist 1693 5.3.1 The cardiologist in general practice: consultant role 1694 5.3.2 Implementing evidence-based medicine 1694 5.3.3 Improving healthcare using electronic records 1694 5.4 Primary care-based self-help programmes 1694 5.5 Hospital-based programmes: hospital services 1695 5.5.1 Evidence-based discharge recommendations necessary for optimal therapy 1695 5.5.2 Systematic quality improvement programmes are essential 1695 5.6 Hospital-based programmes: specialized prevention centres 1696 5.6.1 Cardiac rehabilitation centres help improve lifestyle 1696 5.6.2 Cardiac rehabilitation is cost-effective 1696 5.6.3 Challenges for cardiac rehabilitation: female gender and co-morbidities 1696 5.6.4 Repeated sessions improve compliance 1697 5.7 Non-governmental organization programmes 1697 5.8 Action at the European political level 1697 References 1698 1638 Abbreviations and acronyms ABI ACCORD ADVANCE ankle– brachial index Action to Control Cardiovascular Risk in Diabetes Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE Appraisal of Guidelines Research and Evaluation AHA American Heart Association apoA1 apolipoprotein A1 apoB apolipoprotein B CABG coronary artery bypass graft surgery CARDS Collaborative AtoRvastatin Diabetes Study CCNAP Council on Cardiovascular Nursing and Allied Professions CHARISMA Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD coronary heart disease CKD chronic kidney disease COMMIT Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP C-reactive protein CURE Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD cardiovascular disease DALYs disability-adjusted life years DBP diastolic blood pressure DCCT Diabetes Control and Complications Trial ED erectile dysfunction eGFR estimated glomerular filtration rate EHN European Heart Network EPIC European Prospective Investigation into Cancer and Nutrition EUROASPIRE European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR glomerular filtration rate GOSPEL Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE Grading of Recommendations Assessment, Development and Evaluation HbA1c glycated haemoglobin HDL high-density lipoprotein HF-ACTION Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT Hypertension Optimal Treatment Study HPS Heart Protection Study HR hazard ratio hsCRP high-sensitivity C-reactive protein HYVET Hypertension in the Very Elderly Trial ICD International Classification of Diseases IMT intima-media thickness INVEST International Verapamil SR/Trandolapril JTF Joint Task Force LDL low-density lipoprotein Lp(a) lipoprotein(a) LpPLA2 lipoprotein-associated phospholipase Joint ESC Guidelines LVH MATCH left ventricular hypertrophy Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD Modification of Diet in Renal Disease MET metabolic equivalent MONICA Multinational MONItoring of trends and determinants in CArdiovascular disease NICE National Institute of Health and Clinical Excellence NRT nicotine replacement therapy NSTEMI non-ST elevation myocardial infarction ONTARGET Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA obstructive sleep apnoea PAD peripheral artery disease PCI percutaneous coronary intervention PROactive Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV pulse wave velocity QOF Quality and Outcomes Framework RCT randomized clinical trial RR relative risk SBP systolic blood pressure SCORE Systematic Coronary Risk Evaluation Project SEARCH Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP Systolic Hypertension in the Elderly Program STEMI ST-elevation myocardial infarction SU.FOL.OM3 SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur Systolic Hypertension in Europe TNT Treating to New Targets UKPDS United Kingdom Prospective Diabetes Study VADT Veterans Affairs Diabetes Trial VALUE Valsartan Antihypertensive Long-term Use VITATOPS VITAmins TO Prevent Stroke VLDL very low-density lipoprotein WHO World Health Organization What is cardiovascular disease prevention? 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur It remains the major cause of premature death in Europe, even though CVD mortality has fallen considerably over recent decades in many European countries It is estimated that 80% of all CVD mortality now occurs in developing countries CVD causes mass disability: within the coming decades the disability-adjusted life years (DALYs) estimate is expected to rise from a loss of 85 million DALYs in 1990 to a loss of 150 million DALYs globally in 2020, thereby remaining the leading somatic cause of loss of productivity.1 1639 Joint ESC Guidelines CVD is strongly connected to lifestyle, especially the use of tobacco, unhealthy diet habits, physical inactivity, and psychosocial stress.2 The World Health Organization (WHO) has stated that over three-quarters of all CVD mortality may be prevented with adequate changes in lifestyle CVD prevention, remaining a major challenge for the general population, politicians, and healthcare workers alike, is defined as a co-ordinated set of actions, at public and individual level, aimed at eradicating, eliminating, or minimizing the impact of CVDs and their related disability The bases of prevention are rooted in cardiovascular epidemiology and evidence-based medicine.3 The aim of the 2012 guidelines from the Fifth Joint Task Force (JTF) of the European Societies on Cardiovascular Disease Prevention in Clinical Practice is to give an update of the present knowledge in preventive cardiology for physicians and other health workers The document differs from 2007 guidelines in several ways: there is a greater focus on new scientific knowledge The use of grading systems [European Society of Cardiology (ESC) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE)] allows more evidence-based recommendations to be adapted to the needs of clinical practice The reader will find answers to the key questions of CVD prevention in the five sections: what is CVD prevention, why is it needed, who should benefit from it, how can CVD prevention be applied, and when is the right moment to act, and finally where prevention programmes should be provided A literature search of clinical guidelines aimed at cardiovascular risk assessment in clinical practice identified 1900 publications.4 When these were evaluated using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument, only seven achieved the level considered ‘considerable rigour’ Too much guidance and too little impact? The gap between state-of-the-art knowledge and its implementation in clinical practice remains wide, as shown in recent surveys such as EUROASPIRE III.5 Family doctors may be flooded with recommendations in the wide field of family medicine Finding time to read and implement the many guidelines can be an overwhelming task in a busy primary care centre or a regional hospital clinic The Task Force behind the 2012 recommendations has chosen to limit the size to the level of the executive summary of previous JTF publications All relevant reference material is available on the dedicated CVD Prevention Guidelines page of the ESC Website (www.escardio.org/guidelines) A one-page summary of all strong recommendations according to the GRADE system will be provided, which may stimulate implementation; and a pocket version will be available for daily clinical use 1.2 Development of guidelines The first joint recommendations (1994) reflected the need for a consensus statement from the ESC, the European Atherosclerosis Society, and the European Society of Hypertension, and advocated the principle of total risk assessment for primary prevention A revision was published in 1998 by the second JTF involving these three societies joined by the European Society of General Practice/Family Medicine, the European Heart Network (EHN), and the International Society of Behavioural Medicine Appreciating that an even broader field of expertise was required, the third JTF was extended to include eight societies: the European Association for the Study of Diabetes and the International Diabetes Federation Europe joined The third JTF widened the guidance from coronary heart disease (CHD) to CVD and introduced the concept of total CVD risk assessment using the database of the Systematic Coronary Risk Evaluation Project (SCORE) Special risk charts based on SCORE were produced for both low- and high-risk countries and gained wide acceptance throughout Europe The concept of primary and secondary prevention was replaced by the recognition that atherosclerosis was a continuous process Priorities were proposed at four levels: patients with established disease, asymptomatic individuals at high risk of CVD mortality, first-degree relatives of patients with premature CVD, and other individuals encountered in routine clinical practice In the 2007 update, the fourth JTF reflected consensus from nine scientific bodies as the European Stroke Initiative joined the group From the ESC, the European Association for Cardiovascular Prevention & Rehabilitation contributed with scientists from the fields of epidemiology, prevention, and rehabilitation Novelties were an increased input from general practice and cardiovascular nursing, being key players in the implementation of prevention Lifestyle counselling was given greater importance and there was a revised approach to CVD risk in the young, using a SCORE-based relative risk chart The present update from the fifth JTF reflects the consensus on the broader aspects of CVD prevention from the nine participating organizations For more detailed guidance, reference is made to the specific guidelines from the participating societies, which are in full congruence with this publication The partner societies co-operate in the Joint Societies Implementation Committee, which aims to stimulate dissemination of the guidelines, acceptance at national levels, and the formation of national alliances to translate the recommendations into clinical practice The programme ‘Call for Action’ was one of the efforts of this committee.6 Implementation has been well accepted at the European Union (EU) political level after the launch of the European Heart Health Charter in the European Parliament in June 2007.6 This public health statement has been endorsed by a majority of the EU member states, defining the characteristics of people who tend to stay healthy as: † † † † † † † † No use of tobacco Adequate physical activity: at least 30 five times a week Healthy eating habits No overweight Blood pressure below 140/90 mmHg Blood cholesterol below mmol/L (190 mg/dL) Normal glucose metabolism Avoidance of excessive stress 1.3 Evaluation methods Good guidelines are a major mechanism for improving the delivery of healthcare and improving patient outcomes.7 Guidelines based on credible evidence are more likely to be implemented in clinical 1640 Joint ESC Guidelines Table Classes of recommendations Classes of recommendations Suggested wording to use Class I Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective Class II Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure Is recommended/is indicated Class IIa Weight of evidence/opinion is in favour of usefulness/efficacy Should be considered Class IIb Usefulness/efficacy is less well established by evidence/opinion May be considered Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful Is not recommended Class III Table Definition Levels of evidence Level of evidence A Data derived from multiple randomized clinical trials or meta-analyses Level of evidence B Data derived from a single randomized clinical trial or large non-randomized studies Level of evidence C Consensus of opinion of the experts and/ or small studies, retrospective studies, registries practice.8 The present guidelines follow the quality criteria for development of guidelines, which can be found at www.escardio.org/ knowledge/guidelines/rules In short, experts from the nine organizations performed a comprehensive review and a critical evaluation of diagnostic and therapeutic procedures, including assessment of the risk–benefit ratio The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to the ESC recommendations (Tables and 2) Statements from the writing panel disclosing conflicts of interest are available on the ESC website Changes in conflicts of interest that arose during the writing period were notified The preparation and publication of the fifth JTF report was supported financially by the ESC without any involvement of the pharmaceutical industry Once the document had been finalized by the fifth JTF experts it was submitted for extensive independent external review Following this revision and after acceptance by the ESC Committee for Practice Guidelines and the co-operating organizations in the fifth JTF, the document was published 1.4 Combining evaluation methods An important novelty in reviewing quality of evidence and making recommendations is the use of both the ESC-recommended method of evaluation and the GRADE rating system.9 In contrast to the 2007 guidelines, the JTF has chosen to provide guidance with both systems so that readers acquainted with the former method and those preferring GRADE will find their individually adapted but still congruent guidance in the combined recommendation tables The JTF introduced GRADE as it uses a transparent and rigorous process to assess the quality of evidence in terms of whether further research would or would not change confidence in the estimate of intervention effects or diagnostic accuracy.10 Specific quality indicators are: study limitations; inconsistency of findings; indirectness of evidence; imprecision; and publication bias (Table 3) These are Table Quality of evidence used in GRADE9 Study limitations Non-concealment of allocation; non-blinding of outcome assessment; high losses to follow-up; no intention-to-treat analysis Inconsistent findings Variability due to differences in patients studied, intervention, outcomes assessed Indirectness of evidence Head-to-head comparisons are direct; intervention A vs control and B vs control is indirect in assessing A vs B Imprecision Small patient numbers resulting in wide confidence intervals Publication bias Typically trials showing no effect of intervention are not published or are published in local non-indexed journals 1641 Joint ESC Guidelines applied to each outcome of critical importance for decision-making in the judgement of the guideline group (e.g reduction in clinical events is usually critical; changes in biochemical values are not usually critical) Judgements are then made on these indicators to rate evidence quality from high (i.e further research is unlikely to change confidence in the estimate of effect), to moderate, low, and very low (i.e any estimate of effect is very uncertain) This judgement is made on quality of evidence for the critical outcomes and not those that are not critical for decision-making The value of this new approach is that systematic review or randomized control trial (RCT) evidence that is biased, inconsistent, or imprecise may be downgraded from high- to moderate- or lowquality evidence Similarly, observational data from cohort or case–control studies may be upgraded from moderate or low (as is typical in the old levels-of-evidence approach) to high if bias is unlikely, and findings are consistent and precise This is very helpful in assessing evidence for CVD prevention where RCTs of health behaviours are difficult to conduct and may be misleading GRADE also distinguishes quality of evidence and strength of recommendation.9 Strong evidence does not automatically lead to a strong recommendation Recommendations are based on the quality of the evidence, the degree of uncertainty about the balance of benefits and harms of the intervention, uncertainty about the values and preferences of patients, and uncertainty about whether the intervention is a wise use of resources Rather than have a range of classes of recommendation (e.g Class I– Class III), GRADE only uses two categories—strong or weak (i.e discretionary, conditional) The implications of a strong recommendation are: most informed patients would choose the recommended intervention (and request discussion if not offered); clinicians would ensure that most patients should receive the intervention; and the recommendation would be adopted as policy in organized healthcare systems In contrast, for weak recommendations, some patients would want the intervention but many would not; clinicians would help patients make choices dependent on their values and preferences; policy makers would require debate among various stakeholders to decide on the role of the intervention The GRADE approach can be applied to diagnostic strategies in the same way with a few minor changes to the quality criteria used,9 and may also be used in conjunction with appraisals of resource use and cost-effectiveness.10 However, as resources are valued differently across Europe, it is not feasible in these guidelines to make judgements about the appropriateness of resource use for the interventions and diagnostic strategies considered here Why is prevention of cardiovascular disease needed? Key messages † Atherosclerotic CVD, especially CHD, remains the leading cause of premature death worldwide † CVD affects both men and women; of all deaths that occur before the age of 75 years in Europe, 42% are due to CVD in women and 38% in men † CVD mortality is changing, with declining age-standardized rates in most European countries, which remain high in Eastern Europe † Prevention works: 50% of the reductions seen in CHD mortality relate to changes in risk factors, and 40% to improved treatments † Preventive efforts should be lifelong, from birth (if not before) to old age † Population and high-risk preventive strategies should be complementary; an approach limited to high-risk persons will be less effective; population education programmes are still needed † Despite gaps in our understanding, there is ample evidence to justify intensive public health and individual preventive efforts † There is still substantial room for improvement in risk factor control, even in individuals at very high risk 2.1 Scope of the problem ‘Coronary heart disease (CHD) is now the leading cause of death worldwide; it is on the rise and has become a true pandemic that respects no borders’ This statement from 2009 on the website of the WHO11 does not differ much from the warning issued in 1969 by its Executive Board: ‘Mankind’s greatest epidemic: CHD has reached enormous proportions striking more and more at younger subjects It will result in coming years in the greatest epidemic mankind has faced unless we are able to reverse the trend by concentrated research into its cause and prevention’.12 The second major CVD—stroke—is another substantial cause of death and disability For these reasons, the fifth JTF guidelines refer to the total burden of atherosclerotic CVD The choice of total burden of atherosclerotic CVD may give the impression that nothing has changed over the past 40 years, but this is not true On the contrary, the epidemic has been and still is extremely dynamic and is influenced by both changes in cardiovascular risk factors and in increased opportunities for targeted interventions to prevent and treat CVD This results in ups and downs of cardiovascular morbidity and mortality over relatively short periods with wide variability across the globe, including developing countries where the major proportion of all events occurs nowadays In different parts of the world, the dynamics of the epidemic vary greatly in pattern, magnitude, and timing.13 In Europe, the burden remains high: CVD remains a major cause of premature deaths and loss of DALYs—a composite of premature death and living with the disease It is not widely appreciated that CVD is the main cause of premature death in women: CVD was responsible for 42% of all deaths below 75 years of age in European women and for 38% of all deaths at ,75 years in men.14 However, a decline in age-standardized CHD and CVD mortality has been observed in many European countries between the 1970s and 1990s, with the earliest and most prominent decrease in the more affluent countries, illustrating the potential for prevention of premature deaths and for prolonging healthy life 1642 expectancy In several eastern European countries, however, CVD and CHD mortality remains high.15 Policy makers need to know whether major contributors to morbidity and mortality such as CVD are tracking up or down A valid and actual description of the epidemic by place, time, and personal characteristics is continuously needed to guide and support health policies At present there is no standardized source of Europe-wide CVD morbidity data Results from the Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) project indicated a heterogeneous trend in CHD incidence in the 1980s to 1990s in Europe.16 This pattern may have changed, and results from recent reports suggest that mortality and morbidity from CHD is levelling, especially in younger adults.17,18 One should also realize that because of an ageing population and a reduced case fatality of acute coronary events, the total number of people living with CHD increases The majority of these patients develop the disease at an advanced age, leading to a compression of morbidity in the very old of the community and to a prolonged life expectancy in good health The Global Health Observatory database of the WHO (http://apps.who.int/ghodata/?vid=2510) provides data on present mortality rates from CVD in the world 2.2 Prevention of cardiovascular disease: a lifelong approach Prevention of CVD ideally starts during pregnancy and lasts until the end of life In daily practice, prevention efforts are typically targeted at middle-aged or older men and women with established CVD (i.e secondary prevention) or those at high risk of developing a first cardiovascular event [e.g men and women with combinations of smoking, elevated blood pressure (BP), diabetes or dyslipidaemia (i.e primary prevention)]; CVD prevention in the young, the very old, or those with just a moderate or mild risk is still limited, but can result in substantial benefit Prevention is typically categorized as primary or secondary prevention, although in CVD the distinction between the two is arbitrary in view of the underlying, gradually developing atherosclerotic process Since the instruction by Geoffrey Rose decades ago, two approaches towards prevention of CVD are considered: the population strategy and the high-risk strategy.19 The population strategy aims at reducing the CVD incidence at the population level through lifestyle and environmental changes targeted at the population at large This strategy is primarily achieved by establishing ad-hoc policies and community interventions Examples include measures to ban smoking and reduce the salt content of food The advantage is that it may bring large benefits to the population although it may offer little to the individual The impact of such an approach on the total number of cardiovascular events in the population may be large, because all subjects are targeted and a majority of events occur in the substantial group of people at only modest risk In the high-risk approach, preventive measures are aimed at reducing risk factor levels in those at the highest risk, either individuals without CVD at the upper part of the total cardiovascular risk distribution or those with established CVD Although individuals targeted in this strategy are more likely to benefit from the Joint ESC Guidelines preventive interventions, the impact on the population level is limited, because people at such high risk are few For a long time the population strategy has been considered to be more costeffective than the high-risk approach but since the introduction of highly effective lipid lowering drugs, improvement in smoking cessation programmes and lower costs of antihypertensive drugs, the effectiveness of the high risk approach has increased.20 There is consensus that the largest preventive effect is achieved when these are combined Importantly, evidence that increased cardiovascular risk starts developing at a (very) young age has accumulated over past decades Even exposure to risk factors before birth may influence the lifetime risk of CVD,21 as has been illustrated from studies in the offspring of women who were pregnant during the Dutch famine in the Second World War.22 Although children are at very low absolute risk of developing CVD, those at a relatively high risk compared with their peers remain at increased risk of experiencing a cardiovascular event later in life because of ‘tracking’ of risk factors (i.e those at the high end of the distribution of a risk factor in early life tend to stay in the upper part of the distribution).23 Thus a healthy lifestyle in the young is crucial, although ethical and other reasons prohibit the provision of strong levels of evidence based on randomized trials for the benefits in terms of reduced incidence of CVD from, for example, school programmes on health education or smoking cessation actions Also, the limited attention on CVD prevention in the elderly has proven unjustified Studies have shown that preventive measures (i.e BP lowering and smoking cessation) are beneficial up to advanced age.24,25 These facts exemplify that prevention of CVD should be a lifelong effort, albeit that the beneficial effects in terms of, for example, a lower incidence of fatal or non-fatal cardiovascular events or improvement in quality of life, should always be weighed against the potential harm that specific measures may cause (including side effects of drugs and psychological effects of labelling healthy subjects as patients) and against related costs 2.3 Prevention of cardiovascular disease pays off In order to interpret the dynamics of the CVD epidemic, it is important to differentiate the effect of a reduced case fatality and changes related to preventing clinical events Some authors credit the greater use of evidence-based medical therapies such as thrombolysis, aspirin, angiotensin-converting enzyme (ACE) inhibitors, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery,26,27 while others credit improved management of major risk factors such as smoking, hypertension, and dyslipidaemia.28 The MONICA project, performed during the 1980s and 1990s, showed that only part of the variation in the time trends of coronary event rates could be predicted by trends in risk factors.16 The relationship between changes in risk factor scores and changes in event rates was substantial and the changes in risk factors explained almost half the variation in event rates in men but less in women Moreover, there was a significant association between treatment change and case fatality Thus it was concluded that both primary 1643 Joint ESC Guidelines Treatments United States, '68–'76 40 New Zealand, '74–'81 40 The Netherlands, '78–'85 24 35 IMPACT Scotland, '75–'94 35 IMPACT Sweden, '86–'02 10 60 10 55 38 52 40 IMPACT United States, '80–'00 IMPACT Finland, '82–'97 44 50 76 IMPACT New Zealand, '82–'93 IMPACT Italy, '80–'00 60 43 IMPACT England & Wales, '81–'00 Unexplained 54 46 United States, '80–'90 Finland, '72–'92 Risk factors 10 55 47 23 44 53 36 0% 55 50% 24 100% Figure Percentage of the decrease in deaths from coronary heart disease attributed to treatments and risk factor changes in different populations (adapted from Di Chiara et al 31) prevention and treatment of cardiovascular events influence mortality In many MONICA centres there were quite substantial changes, up or down, in CVD events within time periods as small as 10 years The only reasonable explanation is that both environmental changes, especially related to lifestyle, and improved management are important Another approach to understanding the changes in CVD mortality and incidence rates is by applying models such as the IMPACT mortality model.29 Based on information on changes in coronary risk factors and in treatment as obtained from the results of RCTs regarding the effectiveness of different treatment modalities, it estimates the expected influence on CHD mortality by age and gender This model has been applied in different countries; the results from these studies are rather consistent and similar to what has been observed in other studies of the same subject, as summarized in Figure Beneficial reductions in major risk factors—in particular smoking, BP, and cholesterol—accounted for more than half of the decrease in CHD deaths, although they were counteracted by an increase in the prevalence of obesity and type diabetes; 40% of the decline in CHD death rates is attributed to better treatments of acute myocardial infarction, heart failure, and other cardiac conditions Results from clinical trials and natural experiments also show that a decline in CHD mortality can happen rapidly after individual or population-wide changes in diet or smoking.30 The potential for prevention based on healthy lifestyles, appropriate management of classical risk factors, and selective use of cardioprotective drugs is obvious The human and economic arguments in favour of CVD prevention were recently estimated by the National Institute for Health and Clinical Excellence (NICE)32 as overwhelmingly positive, and many committees from other countries have almost the same views.33 According to the report of NICE, implementation of the population approach may bring numerous benefits and savings: † Narrowing the gap in health inequalities † Cost savings from the number of CVD events avoided † Preventing other conditions such as cancer, pulmonary diseases, and type diabetes † Cost savings associated with CVD such as medications, primary care visits, and outpatient attendances † Cost savings to the wider economy as a result of reduced loss of production due of illness in those of working age, reduced benefit payments, and reduced pension costs from people retiring early from ill health † Improving the quality and length of people’s lives 2.4 Ample room for improvement Within the scope of the comprehensive programme on CVD prevention of the ESC, surveys are carried out to document how well the guidelines are implemented in clinical practice These surveys are called EUROASPIRE; the results from the hospital arm of EUROASPIRE III33 (2006–2007) in 8966 patients with established CHD from 22 European countries show that large proportions of patients still not achieve the lifestyles, risk factor levels, and therapeutic targets set in 2003 by the third JTF The proportions of patients who were at goal for the different recommendations and for risk factor management are given in Table 4; ideally, 100% of patients should reach the goals, but in practice fewer than half tend to reach the targets Moreover, the changes between EUROASPIRE I (1996) and EUROASPIRE III reveal that the proportion of smokers did not 1644 Joint ESC Guidelines Table Guideline recommendations vs achievements in patients with established coronary heart disease in EUROASPIRE III Who should benefit from it? 3.1 Strategies and risk estimation Key messages* Guideline recommendations Proportions at goal Smoking cessation among smokers 48 Regular physical activity 34 BMI